Nesidioblastosis and Subsequent Diabetes Mellitus in a Dog with Hyperinsulinemic Hypoglycemia Treated with Partial Pancreatectomy.

A 6.5 yr old castrated male mixed-breed dog was presented for clinical signs associated with hypoglycemia. Hyperinsulinemic hypoglycemia was diagnosed as the cause of the persistent hypoglycemia. No obvious pancreatic mass was seen on abdominal computed tomography and exploratory laparotomy. A partial pancreatectomy was performed with the suspicion of an insulinoma-causing hyperinsulinemic hypoglycemia. Nesidioblastosis was diagnosed based clinical, biochemical, and histopathologic findings. There was beta cell hyperplasia and no evidence of neoplasia. The dog was euglycemic postoperatively after a partial pancreatectomy. Long-term follow-up after 2 yr revealed that the dog was diagnosed with diabetes mellitus.

Evaluation of plasma cortisol during fasting test in patients with endogenous hyperinsulinemic hypoglycemia. Fifteen years experience.

BACKGROUND: Endogenous hyperinsulinemic hypoglycemia (EHH) is a rare clinical condition. The aim of this study was to evaluate baseline plasma cortisol concentration and its concentration during hypoglycemic crisis in fasting tests (FT) performed in our center. Secondarily, the aim was to establish the relationship between baseline cortisol and the time of evolution of EHH. MATERIAL AND METHODS: A retrospective, observational, descriptive study was carried out which included patients with hypoglycemic disorder with positive FT. RESULTS: Of a total of 21 patients, 16 presented insulinoma, 1 nesidioblastosis, 2 malignant insulinoma and 2 EHH without pathological diagnosis. The time from the onset of symptoms to diagnosis was 2 years (Q1=1.5-Q2=5.5). The comparison between median baseline cortisol (BC)=11.8 mcg/dl (nmol/L 340.68) (Q1=9-Q3=14.1) and median cortisol during hypoglycemic episode (HC)=11.6 mcg/dl (nmol/L: 303.44) (Q1=7.8-Q3=16.1) showed no differences (Z=-0.08; P>.05). When correlating BC with HC, no significant relationship was observed (r=0.16; P>.05). When correlating the glycemic value in the crisis and the HC, a slight negative trend was found (r=-0.53; P=.01). In addition, we found that recurrent hypoglycemic disorder is associated with lower baseline cortisol values ​​the longer the time of its evolution. CONCLUSION: We confirmed that cortisol values ​​remain low during hypoglycemic episodes, reinforcing the hypothesis of lack of response of this counterregulatory hormone in cases of recurrent hypoglycemia.

Circularity of islets is a distinct marker for the pathological diagnosis of adult non-neoplastic hyperinsulinemic hypoglycemia using surgical specimens.

BACKGROUND: Adult non-neoplastic hyperinsulinemic hypoglycemia (ANHH), also known as adult-onset nesidioblastosis, is a rare cause of endogenous hyperinsulinemic hypoglycemia in adults. This disease is characterized by diffuse hyperplasia of pancreatic endocrine cells and is diagnosed by a pathological examination. While diagnostic criteria for this disease have already been proposed, we established more quantitative criteria for evaluating islet morphology. METHODS: We measured the number, maximum diameter, total area, and circularity (representing how closely islets resemble perfect spheres) of islets contained in representative sections of ANHH (n = 4) and control cases (n = 5) using the NIS-Elements software program. We also measured the average cell size, percentage of cells with enlarged nuclei, and percentage of cells with recognizable nucleoli for each of three representative islets. We also assessed the interobserver diagnostic concordance of ANHH between five experienced and seven less-experienced pathologists. RESULTS: There was no significant difference in the number, maximum diameter, or total area of islets between the two groups, even after correcting for these parameters per unit area. However, the number of islets with low circularity (< 0.71) per total area of the pancreatic parenchyma was significantly larger in ANHH specimens than in controls. We also found that the percentage of cells with recognizable nucleoli was significantly higher in the ANHH group than in the controls. There were no significant differences in the average cell size or the number of cells with enlarged nuclei between the groups. The correct diagnosis rate with the blind test was 47.5% ± 6.12% for experienced pathologists and 50.0% ± 8.63% for less-experienced pathologists, with no significant differences noted. CONCLUSIONS: Low circularity, which indicates an irregular islet shape, referred to as "irregular shape and occasional enlargement of islets" and "lobulated islet structure" in a previous report, is a useful marker for diagnosing ANHH. An increased percentage of recognizable nucleoli, corresponding to "macronucleoli in ß-cells," has potential diagnostic value.

Drug-induced hyperinsulinemic hypoglycemia: An update on pathophysiology and treatment.

The initial step for the differential diagnosis of hypoglycemia is to determine whether it is hyperinsulinemic or non hyperinsulinemic. Existing literature discusses drug-related hypoglycemia, but it misses a focus on drug-induced hyperinsulinemic hypoglycemia (DHH). Here we reviewed the association existing between drugs and hyperinsulinemic hypoglycemia. We primarily selected on the main electronic databases (MEDLINE, EMBASE, Web of Science, and SCOPUS) the reviews on drug-induced hypoglycemia. Among the drugs listed in the reviews, we selected the ones linked to an increase in insulin secretion. For the drugs missing a clear association with insulin secretion, we investigated the putative mechanism underlying hypoglycemia referring to the original papers. Our review provides a list of the most common agents associated with hyperinsulinemic hypoglycemia (HH), in order to facilitate both the recognition and the prevention of DHH. We also collected data about the responsiveness of DHH to diazoxide or octreotide.

Concurrence of hyperinsulinemia and hyperuricemia significantly augmented all-cause mortality.

BACKGROUND AND AIMS: Hyperinsulinemia and hyperuricemia are known to increase the risk of mortality due to certain complications, such as Type 2 Diabetes and cardiovascular disease. However, despite their common comorbidities, their combined effect has not been evaluated. The study's aim was to evaluate the combine effect of hyperinsulinemia and hyperuricemia on all-cause mortality. METHODS AND RESULTS: NHANES datasets (cycles 2003-2018) were examined. Differences between groups were evaluated using Rao-Scott Chi-square and General Linear Model for categorical and continuous data, respectively. Hazard Ratios (HR) were calculated using Cox regression with 95% confidence intervals (95%CI). There was significant difference (p < 0.05) in the mortality rate between the control group (2.3 ± 0.2%), the hyperinsulinemia only group (3.1 ± 0.3%), the hyperuricemia only group (4.0 ± 0.8%), and both conditions (5.1 ± 0.8%). Individually, when compared to the control group, there was a significant increase in mortality risk for hyperinsulinemia (HR: 1.50, 95%CI: 1.12-2.01, p = 0.007) and hyperuricemia (HR: 1.80, 95%CI:1.18-2.75, p = 0.006). However, when both conditions were present, there appeared an additive effect in the mortality risk (HR: 2.32, 95%CI: 1.66-3.25, p < 0.001). When stratified by BMI class, only normal weight participants presented with a significant risk (HR: 7.00, 95%CI: 2.50-20.30, p < 0.001). Also, when stratified by age, only participants older than 40 years presented a risk (HR: 2.22, 95%CI: 1.56-3.16, p < 0.001). CONCLUSION: Alone, hyperuricemia and hyperinsulinemia significantly increased the mortality rate; however, the combined presence of both pathologies was associated with a significantly augmented mortality rate. Normal weight participant or that were >40 years old had a greater risk for mortality.

The Relationship between Insulin Resistance and Thyroid Volume in Georgia.

Patients with insulin resistance (IR) have a higher thyroid volume therefore the aim of our study is to examine the correlation between IR and thyroid volume in the residents of Georgia. METHODS: 413 patients with a mean age of 37.3 ± and 11.4 years were included in this study. Out of those, 120 were males, and 293 were females who were studied retrospectively. They had hyperinsulinemia and were referred to the clinic from 2017 to 2019. The factors studied were age, sex, body mass index (BMI), clinical signs, thyroid ultrasound, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipids, fasting insulin, fasting glucose, thyroid stimulating hormone (TSH), Free thyroxine (FT4), and Zinc (Zn). RESULTS: IR was detected in 252 individuals. The frequency of men with insulin resistance was significantly higher than in the control group - 72.50%, and 56.31%, respectively (F = 9.55, p= 0.0021). Mean thyroid volume in the patients with IR was significantly higher compared to the controls 20.52 + 6.39 cm3 and 15.25 + 6.55 cm3, respectively (p < 0.001). Hyperinsulinemia had a significant positive correlation with Goiter r = 0.445, p < 0.0001. The associated factors for hyperinsulinemia are: Goiter (1) - OR = 5.12 (95% CI:3.02-8.69); Cholesterol - OR = OR = 3.31 (95% CI: 1.54-7.14); Triglycerides - OR = 3.23 (95% CI:1.02-10.28); Obesity (1)- OR = 3.94 (95% CI: 2.23-6.98); Thyroid structural changes (1) - OR = 2.01 (95% CI: 1.12-3.60); ALT/AST-OR = 4.53 (95% CI: 2.33-8.80); Zn decreased Odds Ratio hyperinsulinemia - OR = 0.95 (95% CI: 0.94-0.97). CONCLUSION: Hyperinsulinemia is the most common cause of diffuse goiter and the heterogeneous structure of the thyroid. The volume of the thyroid gland shows a significant positive association with the characteristics of metabolic syndrome and increased thyroid volume predictors of metabolic syndrome.

C-peptide level concomitant with hypoglycemia gives better performances than insulin for the diagnosis of endogenous hyperinsulinism: a single-center study of 159 fasting trials.

INTRODUCTION: Diagnosis of endogenous hyperinsulinism relies on the occurrence of a hypoglycemia, concomitant with inadequate high insulin and C-peptide levels. However, diagnostic cutoffs are not consensual among the different learned societies. The objective of this work was to propose optimized cutoffs for these three parameters for the diagnosis of endogenous hyperinsulinism. METHODS: All the patients having performed a fasting trial in Cochin Hospital Endocrinology Department between February 2012 and August 2022 were included. The results of glycemia, insulin and C-peptide levels during fasting trial were collected and analyzed. RESULTS: One hundred and fifty-nine patients were included: 26 with endogenous hyperinsulinism and 133 without endogenous hyperinsulinism. ROC analysis of glycemia nadir during fasting trial identified the value of 2.3 mmol/L as the optimal cutoff, ensuring a sensitivity of 100% associated with a specificity of 81%. ROC analysis of insulin and C-peptide levels concomitant with hypoglycemia <2.3 mmol/L showed very good diagnostic performances of both parameters with respective cutoffs of 3.1 mUI/L (=21.5 pmol/L; sensitivity = 96%; specificity = 92%) and 0.30 nmol/L (sensitivity = 96%; specificity = 100%). Insulin to glycemia ratio as well as C-peptide to glycemia ratio (in pmol/mmol) at the time of glycemia nadir did not show better diagnostic performances than C-peptide alone. CONCLUSION: A C-peptide level 0.3 nmol/L concomitant with a hypoglycemia <2.3 mmol/L appears as the best criterion to make the diagnosis of endogenous hyperinsulinism. Insulin level can be underestimated on hemolyzed blood samples, frequently observed in fasting trial, and thus shows lower diagnostic performances.

Hyperinsulinemic Hypoglycemia Diagnosed in Childhood Can Be Monogenic.

CONTEXT: Congenital hyperinsulinism (HI) is characterized by inappropriate insulin secretion despite low blood glucose. Persistent HI is often monogenic, with the majority of cases diagnosed in infancy. Less is known about the contribution of monogenic forms of disease in those presenting in childhood. OBJECTIVE: We investigated the likelihood of finding a genetic cause in childhood-onset HI and explored potential factors leading to later age at presentation of disease. METHODS: We screened known disease-causing genes in 1848 individuals with HI, referred for genetic testing as part of routine clinical care. Individuals were classified as infancy-onset (diagnosed with HI < 12 months of age) or childhood-onset (diagnosed at age 1-16 years). We assessed clinical characteristics and the genotypes of individuals with monogenic HI diagnosed in childhood to gain insights into the later age at diagnosis of HI in these children. RESULTS: We identified the monogenic cause in 24% (n = 42/173) of the childhood-onset HI cohort; this was significantly lower than the proportion of genetic diagnoses in infancy-onset cases (74.5% [n = 1248/1675], P < 0.00001). Most (75%) individuals with genetically confirmed childhood-onset HI were diagnosed before 2.7 years, suggesting these cases represent the tail end of the normal distribution in age at diagnosis. This is supported by the finding that 81% of the variants identified in the childhood-onset cohort were detected in those diagnosed in infancy. CONCLUSION: We have shown that monogenic HI is an important cause of hyperinsulinism presenting outside of infancy. Genetic testing should be considered in children with persistent hyperinsulinism, regardless of age at diagnosis.

Hyperinsulinism-hyperammonemia syndrome in two Peruvian children with refractory epilepsy.

OBJECTIVES: Congenital hyperinsulinism (HI) is a heterogeneous clinical disorder with great variability in its clinical phenotype, and to date, pathogenic variants in 23 genes have been recognized.  Hyperinsulinism-hyperammonemia syndrome (HI/HA) is the second most frequent cause of this disease that shows an autosomal dominant pattern and is caused by an activating mutation of the GLUD1 gene, which responds favorably to the use of diazoxide. HI/HA syndrome presents with fasting hypoglycemia; postprandial hypoglycemia, especially in those with a high protein content (leucine); and persistent mild hyperammonemia. Neurological abnormalities, in the form of epilepsy or neurodevelopmental delay, are observed in a high percentage of patients; therefore, timely diagnosis is crucial for proper management. CASE PRESENTATION: We report the clinical presentation of two Peruvian children that presented with epilepsy whose genetic analysis revealed a missense mutation in the GLUD1 gene, one within exon 11, at 22% mosaicism; and another within exon 7, as well as their response to diazoxide therapy. To the best of our knowledge, these are the first two cases of HI/HA syndrome reported in Peru. CONCLUSIONS: HI/HA syndrome went unnoticed, because hypoglycemia was missed and were considered partially controlled epilepsies. A failure to recognize hypoglycemic seizures will delay diagnosis and adequate treatment, so a proper investigation could avoid irreversible neurological damage.

Modulation of gene expression profile following consumption of high-dairy products in subjects with hyperinsulinemia.

BACKGROUND AND AIM: Dysregulation of gene expression is associated to a higher risk of type 2 diabetes (T2D). Further, research indicates that dairy consumption may potentially affect gene expression. The aim of this study was to examine if genes and pathways associated with T2D are differentially changed in subjects with hyperinsulinemia after high dairy (HD) diet. METHODS AND RESULTS: Ten obese patients with hyperinsulinemia who consumed HD (4 servings/day according to the Canadian Food Guide (2007)) for six weeks participated in this study. Before and after HD consumption, fasting blood samples were collected. Blood was taken in PAX-gene tubes and RNA was extracted and analyzed using Clariom S microarrays. Results indicated that 236 genes (137 up-regulated and 99 down-regulated; fold change (FC) ≥ ±1.2; p < 0.05) were expressed differentially between before and after HD intake. Genes related to pathways associated with insulin signaling and inflammation, such as olfactory receptor activity, G-protein-coupled receptors (GPCR), phosphatidylinositol-3-OHKinase (PI3K)/AKT2 (PI3K-AKT2), Ras signaling, Mitogen-Activated Protein Kinase (MAPK) were altered following HD. CONCLUSION: Overall, results suggest a potential protective effect of HD intake in individuals at risk of T2D through modification of gene expression profiles. REGISTRATION NUMBER FOR CLINICAL STUDIES: NCT02961179.

Endogenous hyperinsulinemic hypoglycemia: case series and literature review.

PURPOSE: Endogenous hyperinsulinemic hypoglycemia (EHH) is an uncommon disease characterized by inappropriately high plasma insulin levels despite low plasma glucose levels. Some rare etiologies can lead to EHH. Correct diagnosis is a prerequisite for treatment. Hence, although challenging, it is crucial for patients with EHH to identify the different causes. METHODS: We describe a case series of three patients, all of whom had obvious hypoglycemic symptoms and extraordinary hyperinsulinemia. Their plasma glucose, insulin, and C-peptide levels were tested simultaneously when hypoglycemia occurred. Moreover, other biochemical indices and relevant antibody levels were measured and imaging examinations were conducted. RESULTS: According to their medical history, physical examination, laboratory results, and imaging findings, the three patients were diagnosed with insulinoma, type B insulin resistance syndrome, and insulin autoimmune syndrome. After precise treatments, hypoglycemia was ultimately eliminated. CONCLUSION: Although these diseases have similar symptoms and biochemical abnormalities, the treatment and prognosis are different. The case series presented here highlights the challenges in the differential diagnosis of EHH. An accurate diagnosis is necessary for hypoglycemia treatment.

[Hypoglycaemia in patients without diabetes mellitus]. / Hypoglykemie bij patiënten zonder diabetes mellitus.

A structured approach in the diagnostic process of hypoglycemia is important to find the right diagnosis. The first step is to recognize the symptoms of hypoglycemia, confirming the hypoglycemia during symptoms and dissolvement of complaints once the glucose level is restored to normal. This confirms the Whipple triad. The second step is to exclude common causes. The third, and most important, step is a diagnostic fasting test. Measurement of insulin and C-peptide during hypoglycemia will guide to exogenic or endogenic causes of hyperinsulinism. Targeted additional investigation is then required. Often the underlying cause is treatable. This justifies the need to measure a well-timed serum glucose when hypoglycemia is suspected to make a quick diagnosis.

Congenital Hyperinsulinemia of Infancy: Role of Molecular Testing in Management and Genetic Counseling.

Congenital hyperinsulinemia (CHI) is a genetically and clinically heterogenous disorder. In addition to the standard care of management of the proband, genetic counseling regarding the risk of recurrence in the future siblings is an important part in the management of the disorder. The counseling needs identification of accurate etiology and is challenging due to the complexity of the molecular mechanisms of CHI. This case highlights the importance of molecular testing which not only helped in planning the management of the proband with CHI but also helped in providing genetic counseling for which the family had consulted the medical genetics department.

Phosphomannomutase 2 hyperinsulinemia: Recent advances of genetic pathogenesis, diagnosis, and management.

Congenital hyperinsulinemia (CHI), is a clinically heterogeneous disorder that presents as a major cause of persistent and recurrent hypoglycemia during infancy and childhood. There are 16 subtypes of CHI-related genes. Phosphomannomutase 2 hyperinsulinemia (PMM2-HI) is an extremely rare subtype which is first reported in 2017, with only 18 families reported so far. This review provides a structured description of the genetic pathogenesis, and current diagnostic and therapeutic advances of PMM2-HI to increase clinicians' awareness of PMM2-HI.

Effectiveness of beinaglutide in a patient with late dumping syndrome after gastrectomy: A case report.

RATIONALE: Dumping syndrome is a frequent and potentially severe complication after gastric surgery. Beinaglutide, a recombinant human glucagon-like peptide-1 (GLP-1) which shares 100% homology with human GLP-1(7-36), has never been reported in the treatment of dumping syndrome before. PATIENT CONCERNS: The patient had undergone distal gastrectomy for gastric signet ring cell carcinoma 16 months ago. He presented with symptoms of paroxysmal palpitation, sweating, and dizziness for 4 months. DIAGNOSIS: He was diagnosed with late dumping syndrome. INTERVENTIONS AND OUTCOMES: The patient was treated with dietary changes and acarbose for 4 months before admitted to our hospital. The treatment with dietary changes and acarbose did not prevent postprandial hyperinsulinemia and hypoglycemia according to the 75 g oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) on admission.Therefore, the patient was treated with beinaglutide 0.1 mg before breakfast and lunch instead of acarbose. After the treatment of beinaglutide for 1 month, OGTT showed a reduction in postprandial hyperinsulinemia compared with before starting treatment, and the time in the range of 3.9 to 10 mmol/L became 100% in CGM. No side effect was observed in this patient during beinaglutide treatment. LESSONS: These findings suggest that beinaglutide may be effective for treating post-gastrectomy late dumping syndrome.

Model-Based Assessment of C-Peptide Secretion and Kinetics in Post Gastric Bypass Individuals Experiencing Postprandial Hyperinsulinemic Hypoglycemia.

Assessment of insulin secretion is key to diagnose postprandial hyperinsulinemic hypoglycemia (PHH), an increasingly recognized complication following bariatric surgery. To this end, the Oral C-peptide Minimal Model (OCMM) can be used. This usually requires fixing C-peptide (CP) kinetics to the ones derived from the Van Cauter population model (VCPM), which has never been validated in PHH individuals. The objective of this work was to test the validity of the OCMM coupled with the VCPM in PHH subjects and propose a method to overcome the observed limitations. Two cohorts of adults with PHH after gastric bypass (GB) underwent either a 75 g oral glucose (9F/3M; age=42±9 y; BMI=28.3±6.9 kg/m2) or a 60 g mixed-meal (7F/3M; age = 43 ± 11 y; BMI=27.5±4.2 kg/m2) tolerance test. The OCMM was identified on CP concentration data with CP kinetics fixed to VCPM (VC approach). In both groups, the VC approach underestimated CP-peak and overestimated CP-tail suggesting CP kinetics predicted by VCPM to be inaccurate in this population. Thus, the OCMM was identified using CP kinetics estimated from the data (DB approach) using a Bayesian Maximum a Posteriori estimator. CP data were well predicted in all the subjects using the DB approach, highlighting a significantly faster CP kinetics in patients with PHH compared to the one predicted by VCPM. Finally, a simulation study was used to validate the proposed approach. The present findings question the applicability of the VCPM in patients with PHH after GB and call for CP bolus experiments to develop a reliable CP kinetic model in this population.

Insulin increases central aortic stiffness in response to hyperglycemia in healthy humans: A randomized four-arm study.

INTRODUCTION: Increasing arterial stiffness is a feature of vascular aging that is accelerated by conditions that enhance cardiovascular risk, including diabetes mellitus. Multiple studies demonstrate divergence of carotid-femoral pulse wave velocity and augmentation index in persons with diabetes mellitus, though mechanisms responsible for this are unclear. MATERIALS AND METHODS: We tested the effect of acutely and independently increasing plasma glucose, plasma insulin, or both on hemodynamic function and markers of arterial stiffness (including carotid-femoral pulse wave velocity, augmentation index, forward and backward wave reflection amplitude, and wave reflection magnitude) in a four-arm, randomized study of healthy young adults. RESULTS: Carotid-femoral pulse wave velocity increased only during hyperglycemic-hyperinsulinemia (+0.36 m/s; p = 0.032), while other markers of arterial stiffness did not change (all p > 0.05). Heart rate (+3.62 bpm; p = 0.009), mean arterial pressure (+4.14 mmHg; p = 0.033), central diastolic blood pressure (+4.16 mmHg; p = 0.038), and peripheral diastolic blood pressure (+4.09 mmHg; p = 0.044) also significantly increased during hyperglycemic-hyperinsulinemia. CONCLUSIONS: Hyperglycemic-hyperinsulinemia acutely increased cfPWV, heart rate, mean arterial pressure, and diastolic blood pressure in healthy humans, perhaps reflecting enhanced sympathetic tone. Whether repeated bouts of hyperglycemia with hyperinsulinemia contribute to chronically-enhanced arterial stiffness remains unknown.

Dietary Patterns of Insulinemia, Inflammation and Glycemia, and Pancreatic Cancer Risk: Findings from the Women's Health Initiative.

BACKGROUND: Pancreatic cancer risk is increasing in countries with high consumption of Western dietary patterns and rising obesity rates. We examined the hypothesis that specific dietary patterns reflecting hyperinsulinemia (empirical dietary index for hyperinsulinemia; EDIH), systemic inflammation (empirical dietary inflammatory pattern; EDIP), and postprandial glycemia [glycemic index (GI); glycemic load (GL)] are associated with pancreatic cancer risk, including the potential modifying role of type 2 diabetes (T2D) and body mass index (BMI). METHODS: We calculated dietary scores from baseline (1993-1998) food frequency questionnaires among 129,241 women, 50-79 years-old in the Women's Health Initiative. We used multivariable-adjusted Cox regression to estimate HRs and 95% confidence intervals (95% CI) for pancreatic cancer risk. RESULTS: During a median 19.9 years of follow-up, 850 pancreatic cancer cases were diagnosed. We observed no association between dietary scores and pancreatic cancer risk overall. However, risk was elevated among participants with longstanding T2D (present >3 years before pancreatic cancer diagnosis) for EDIH. For each 1 SD increment in dietary score, the HRs (95% CIs) were: EDIH, 1.33 (1.06-1.66); EDIP, 1.26 (0.98-1.63); GI, 1.26 (0.96-1.67); and GL, 1.23 (0.96-1.57); although interactions were not significant (all P interaction >0.05). Separately, we observed inverse associations between GI [0.86 (0.76-0.96), P interaction = 0.0068] and GL [0.83 (0.73-0.93), P interaction = 0.0075], with pancreatic cancer risk among normal-weight women. CONCLUSIONS: We observed no overall association between the dietary patterns evaluated and pancreatic cancer risk, although women with T2D appeared to have greater cancer risk. IMPACT: The elevated risk for hyperinsulinemic diets among women with longstanding T2D and the inverse association among normal-weight women warrant further examination.

Hyperinsulinemia during pregnancy across varying degrees of glucose tolerance: An examination of the Kraft database.

AIM: Hyperinsulinemia is a known underlying driver of metabolic disease; however, its role in pregnancy complications is less understood due to insulin measurement not being a part of standard clinical assessments. This study aimed to characterize hyperinsulinemia in pregnancy by gestational diabetes (GD) status using Kraft methodology. METHODS: We analyzed historical data from 926 pregnant women who underwent a 100-g oral glucose tolerance test (OGTT), which included insulin measurement. Subjects were grouped by GD diagnosis status ("Normal", "Borderline", "GD") and insulin responses over 3 h were compared between groups. RESULTS: "GD" was diagnosed in 20.3% of the subjects and 13.8% were grouped as "Borderline." The prevalence of hyperinsulinemia using the Kraft algorithm was 33.1% for Kraft IIB and 42.0% for Kraft III. Compared to normal glucose-tolerant mothers, individuals from the "Borderline" group had an exacerbated insulin response, although not to the same magnitude as those with "GD." CONCLUSIONS: Dynamic OGTT insulin measurement during pregnancy may provide a meaningful assessment of metabolic risk among women who would otherwise not be diagnosed with GD.